Figure 1. DA pedigrees with mutations identified in SLC1A1.

(A) Pedigrees consistent with autosomal recessive inheritance are shown. Filled symbols represent individuals with DA, arrows indicate each proband, and the diagonal line represents a deceased subject. Representative chromatograms from control or DA pedigree DNA, with allele genotype (WT, wildtype; Mut, mutant) indicated. Boxes indicate the location of each mutation. (B) RFLP analysis of DA pedigrees. For c.1333C > T RFLP, AgeI digestion releases 252- and 229-bp fragments (shown as control [C]). The c.1333C > T mutation inactivates the AgeI site, leaving a 481-bp product (top panel). For c.1184–1186delTCA RFLP, BsaBI does not cut the 461-bp PCR product (shown as control). The c.1184-1186delTCA mutation results in a 458-bp amplicon, which is cut by BsaBI into 245- and 213-bp fragments (bottom panel). L, 100-bp ladder. (C) The OCD-associated region at 9p24 containing SLC1A1. The 39-kb region identified in early-onset OCD cohorts is represented by the red line; SLC1A1 coding regions are represented by gray bars; untranslated regions are represented by vertical white bars; blue shading indicates a significant association with OCD (P < 0.05); red shading indicates an experimentally validated loss-of-function mutation; stacked boxes represent SNPs; blue triangles represent markers linked to OCD; connected blue circles indicate haplotype blocks significantly associated with OCD (P < 0.05); lower boxes indicate missense mutations (c.490A > G [T164A, ref. 40]), c.1184–1186delTCA [I395del], c.1333C > T [R445W]); red arrow indicates an association with OCD-like features; and coordinates represent telomeric distance (in Mb). Sex-specific association with OCD is indicated (male [M] or female [F]). Roman numerals correlate with individual OCD studies: i (20); ii (21); iii (26); iv (27); v (25); vi (22); vii (23); and viii (24).